The replication of DNA and chromatin is being studied in isolated nuclei and re-constructed subnuclear systems. Characterization of the replication related DNA polymerase, the identification of the associated activator proteins and the role of cytosol proteins in chromatin replication will be studied. The uptake of histones into chromatin replicated in vitro will be studied in isolated nuclei. Attempts will be made to identify principles of histone-cytosol protein (i.e. replication supporting non-histones) interactions during maturation of newly replicated chromatin. DNA and chromatin replication studies will be extended to Friend Leukemia cells undergoing differentiation. BIBLIOGRAPHIC REFERENCES: Seki, S., and Mueller, G.C. Dissociation and Reconstruction of the DNA Replicase System of HeLa Cell Nuclei. Biochim. Biophys. Acta, 435: 236-250. Planck, S.R., and Mueller, G.C. DNA Chain Growth and Organization of Replicating Units in HeLa Cells. Biochemistry, 16: 1808-1813, 1977.